PMID- 9437658
OWN - NLM
STAT- MEDLINE
DCOM- 19980226
LR  - 20191102
IS  - 1044-7393 (Print)
IS  - 1044-7393 (Linking)
VI  - 32
IP  - 1-3
DP  - 1997 Sep-Dec
TI  - The effects of aging and neurodegeneration on apoptosis-associated DNA 
      fragmentation and the benefits of nicotinamide.
PG  - 59-74
AB  - In this work, the tertiary butylhydroperoxide- (t-BuOOH) treated mouse was used 
      as a model to study the oxidative stress that is associated with various 
      neurodegenerative diseases. DNA was found to be an early target of t-BuOOH 
      attack. Necrosis was associated with extensive DNA fragmentation that occurred in 
      almost all regions of the brain within 20 min following intracerebroventricular 
      (icv) injection of 109.7 mg/kg t-BuOOH. Apoptosis was associated with high levels 
      of DNA fragmentation that was observed at 48 h after icv administration of 21.9 
      mg/kg t-BuOOH. Susceptibility to DNA damage was found to be age-dependent, since 
      24-mo-old mice exhibited consistently higher and more pervasive DNA damage than 8 
      mo-old-mice. Extensive DNA damage was seen in various brain regions in patients 
      with Alzheimer disease (AD) and with both Alzheimer and Parkinson disease 
      (AD-PD). These results directly implicate DNA damage in neurodegeneration. The 
      DNA fragmentation ob-served can lead to both apoptosis and necrosis, as suggested 
      by gel electrophoresis. Nicotinamide, a precursor of NAD in the brain, was able 
      to prevent DNA fragmentation induced by low-dose t-BuOOH, when coadministered 
      with the toxin.
FAU - Mukherjee, S K
AU  - Mukherjee SK
AD  - School of Pharmacy, Department of Molecular Pharmacology and Toxicology, 
      University of Southern California, Los Angeles 90033, USA.
FAU - Adams, J D Jr
AU  - Adams JD Jr
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Chem Neuropathol
JT  - Molecular and chemical neuropathology
JID - 8910358
RN  - 0 (Reactive Oxygen Species)
RN  - 25X51I8RD4 (Niacinamide)
SB  - IM
MH  - Aged
MH  - Aging/*physiology
MH  - Alzheimer Disease/pathology
MH  - Animals
MH  - Apoptosis/drug effects/*physiology
MH  - Brain Chemistry/physiology
MH  - DNA Fragmentation/drug effects/*physiology
MH  - Humans
MH  - Injections, Intraventricular
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Degeneration/*physiopathology/prevention & control
MH  - Niacinamide/*pharmacology
MH  - Parkinson Disease/pathology
MH  - Reactive Oxygen Species/metabolism
EDAT- 1998/01/23 06:09
MHDA- 2001/03/28 10:01
CRDT- 1998/01/23 06:09
PHST- 1998/01/23 06:09 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1998/01/23 06:09 [entrez]
AID - 10.1007/BF02815167 [doi]
PST - ppublish
SO  - Mol Chem Neuropathol. 1997 Sep-Dec;32(1-3):59-74. doi: 10.1007/BF02815167.